Background: Undernutrition remains highly prevalent in low- and middle-income countries, with sub-Saharan Africa and Southern Asia accounting for majority of the cases. Apart from the health and human capacity impacts on children affected by malnutrition, there are significant economic impacts to households and service providers. The aim of this study was to determine the current state of knowledge on costs and cost-effectiveness of child undernutrition treatment to households, health providers, organizations and governments in low and middle-income countries (LMICs). Methods: \u00a0We conducted a systematic review of peer-reviewed studies in LMICs up to September 2019. We searched online databases including PubMed-Medline, Embase, Popline, Econlit and Web of Science. We identified additional articles through bibliographic citation searches. Only articles including costs of child undernutrition treatment were included. Results: We identified a total of 6436 articles, and only 50 met the eligibility criteria. Most included studies adopted institutional/program (45%) and health provider (38%) perspectives. The studies varied in the interventions studied and costing methods used with treatment costs reported ranging between US$0.44 and US$1344 per child. The main cost drivers were personnel, therapeutic food and productivity loss. We also assessed the cost effectiveness of community-based management of malnutrition programs (CMAM). Cost per disability adjusted life year (DALY) averted for a CMAM program integrated into existing health services in Malawi was $42. Overall, cost per DALY averted for CMAM ranged between US$26 and US$53, which was much lower than facility-based management (US$1344). Conclusion: There is a need to assess the burden of direct and indirect costs of child undernutrition to households and communities in order to plan, identify cost-effective solutions and address issues of cost that may limit delivery, uptake and effectiveness. Standardized methods and reporting in economic evaluations would facilitate interpretation and provide a means for comparing costs and cost-effectiveness of interventions.
\n \n\n \n \nIn sub-Saharan Africa, most transmission of mosquito-transmitted diseases, such as malaria or dengue, occurs within or around houses. Preventing mosquito house entry and reducing mosquito production around the home would help reduce the transmission of these diseases. Based on recent research, we make key recommendations for reducing the threat of mosquito-transmitted diseases through changes to the built environment. The mnemonic, DELIVER, recommends the following best practices: (i) Doors should be screened, self-closing and without surrounding gaps; (ii) Eaves, the space between the wall and roof, should be closed or screened; (iii) houses should be Lifted above the ground; (iv) Insecticide-treated nets should be used when sleeping in houses at night; (v) houses should be Ventilated, with at least two large-screened windows to facilitate airflow; (vi) Environmental management should be conducted regularly inside and around the home; and (vii) Roofs should be solid, rather than thatch. DELIVER is a package of interventions to be used in combination for maximum impact. Simple changes to the built environment will reduce exposure to mosquito-transmitted diseases and help keep regions free from these diseases after elimination. This article is part of the theme issue 'Novel control strategies for mosquito-borne diseases'.
\n \n\n \n \nThe genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3-7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
\n \n\n \n \nBackgroundAsymptomatic transmission was found to be the Achilles' heel of the symptom-based screening strategy, necessitating the implementation of mass testing to efficiently contain the transmission of COVID-19 pandemic. However, the global shortage of molecular reagents and the low throughput of available realtime PCR facilities were major limiting factors.MethodsA novel semi-nested and heptaplex (7-plex) RT-PCR assay with melting analysis for detection of SARS-CoV-2 RNA has been established for either individual testing or 96-sample pooled testing. The complex melting spectrum collected from the heptaplex RT-PCR amplicons was interpreted with the support of an artificial intelligence algorithm for the detection of SARS-CoV-2 RNA. The analytical and clinical performance of the semi-nested RT-PCR assay was evaluated using RNAs synthesized in-vitro and those isolated from nasopharyngeal samples.ResultsThe LOD of the assay for individual testing was estimated to be 7.2 copies/reaction. Clinical performance evaluation indicated a sensitivity of 100% (95% CI: 97.83-100) and a specificity of 99.87% (95% CI: 99.55-99.98). More importantly, the assay supports a breakthrough sample pooling method, which makes possible parallel screening of up to 96 samples in one real-time PCR well without loss of sensitivity. As a result, up to 8,820 individual pre-amplified samples could be screened for SARS-CoV-2 within each 96-well plate of realtime PCR using the pooled testing procedure.ConclusionThe novel semi-nested RT-PCR assay provides a solution for highly multiplex (7-plex) detection of SARS-CoV-2 and enables 96-sample pooled detection for increase of testing capacity. .
\n \n\n \n \nBackgroundWe evaluated the validity and reliability of the Neilands sexual stigma scale administered to 871 gay, bisexual, and other men who have sex with men (GBMSM) at two research locations in Kenya.MethodsUsing cross-validation, exploratory factor analysis (EFA) was performed on a randomly selected subset of participants and validated using confirmatory factor analysis (CFA) on the remaining participants. Associations of the initial and final stigma scale factors with depressive symptoms, alcohol use, and other substance use were examined for the entire dataset.ResultsEFA produced a two-factor scale of perceived and enacted stigma. The CFA model fit to the two-factor scale was improved after removing three cross-loaded items and adding correlated errors (chi-squared\u2009=\u200926.5, df 17, p\u2009=\u20090.07). Perceived stigma was associated with depressive symptoms (beta\u2009=\u20090.34, 95% CI 0.24, 0.45), alcohol use (beta\u2009=\u20090.14, 95% CI 0.03, 0.25) and other substance use (beta\u2009=\u20090.19, 95% CI 0.07, 0.31), while enacted stigma was associated with alcohol use (beta\u2009=\u20090.17, 95% CI 0.06, 0.27).ConclusionsOur findings suggest enacted and perceived sexual stigma are distinct yet closely related constructs among GBMSM in Kenya and are associated with poor mental health and substance use.
\n \n\n \n \nABSTRACTBackgroundReporting cumulative antimicrobial susceptibility testing data on a regular basis is crucial to inform antimicrobial resistance (AMR) action plans at local, national and global levels. However, analysing data and generating a report are time-consuming and often require trained personnel. We illustrate the development and utility of an offline, open-access and automated tool that can support the generation of AMR surveillance reports promptly at the local level.MethodsAn offline application to generate standardized AMR surveillance reports from routinely available microbiology and hospital data files was written in the R programming language. The application can be run by a double-click on the application file without any further user input. The data analysis procedure and report content were developed based on the recommendations of the World Health Organization Global Antimicrobial Resistance Surveillance System (WHO GLASS). The application was tested in Microsoft Windows 10 and 7 using open-access example data sets. We then independently tested the application in seven hospitals in Cambodia, Lao People\u2019s Democratic Republic (PDR), Myanmar, Nepal, Thailand, the United Kingdom, and Vietnam.FindingsWe developed the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), which can support clinical microbiology laboratories to analyse their microbiology and hospital data files (in CSV or Excel format) onsite and promptly generate AMR surveillance reports (in PDF and Excel formats). The data files could be those exported from WHONET and/or other laboratory information systems. The automatically generated reports contain only summary data without patient identifiers. The AMASS application is downloadable from www.amass.website. The participating hospitals tested the application and deposited their AMR surveillance reports in an open-access data repository.InterpretationThe AMASS application can be a useful tool to support the generation and sharing of AMR surveillance reports.FundingMahidol Oxford Tropical Medicine Research Unit (MORU) is funded by the Wellcome Trust (Grant no. 106698/Z/14/Z). Oxford University Clinical Research Unit (OUCRU) is funded by the Wellcome Trust (Grant no. 106680/B/14/Z). The investigators are funded by the Wellcome Trust (CL is funded by a Training Research Fellowship [Grant no. 206736] and DL is funded by an Intermediate Training Fellowship [Grant no. 101103]). BSC is funded by the UK Medical Research Council and Department for International Development (Grant no. MR/K006924/1). The funder has no role in the design and conduct of the study, data collection, or analysis and interpretation of the data.
\n \n\n \n \nT cell responses to SARS-CoV-2 following infection and vaccination are less characterised than antibody responses, due to a more complex experimental pathway.We measured T cell responses in 108 healthcare workers (HCWs) using the commercialised Oxford Immunotec T-SPOT Discovery SARS-CoV-2 assay service (OI T-SPOT) and the PITCH ELISpot protocol established for academic research settings. Both assays detected T cell responses to SARS-CoV-2 spike, membrane and nucleocapsid proteins. Responses were significantly lower when reported by OI T-SPOT than by PITCH ELISpot. Four weeks after two doses of either Pfizer/BioNTech BNT162b or ChAdOx1 nCoV-19 AZD1222 vaccine, the responder rate was 63% for OI T-SPOT Panels1\u00a0+\u00a02 (peptides representing SARS-CoV-2 spike protein excluding regions present in seasonal coronaviruses), 69% for OI T-SPOT Panel 14 (peptides representing the entire SARS-CoV-2 spike), and 94% for the PITCH ELISpot assay. The two OI T-SPOT panels correlated strongly with each other showing that either readout quantifies spike-specific T cell responses, although the correlation between the OI T-SPOT panels and the PITCH ELISpot was moderate. The standardisation, relative scalability and longer interval between blood acquisition and processing are advantages of the commercial OI T-SPOT assay. However, the OI T-SPOT assay measures T cell responses at a significantly lower magnitude compared to the PITCH ELISpot assay, detecting T cell responses in a lower proportion of vaccinees. This has implications for the reporting of low-level T cell responses that may be observed in patient populations and for the assessment of T cell durability after vaccination.
\n \n\n \n \nHigher academic institutions in the UK need to drive improvements in equity, diversity, and inclusion (EDI) through sustainable practical interventions. A broad view of inclusivity is based on an intersectional approach that considers race, geographical location, caring responsibilities, disability, neurodiversity, religion, and LGBTQIA+ identities. We describe the establishment of a diverse stakeholder group to develop practical grass-roots recommendations through which improvements can be advanced. We have developed a manifesto for change, comprising six domains through which academic institutions can drive progress through setting short, medium, and long-term priorities. Interventions will yield rewards in recruitment and retention of a diverse talent pool, leading to enhanced impact and output.
\n \n\n \n \nExtension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T\u00a0cell response to the spike protein. NAb levels were higher after the extended dosing interval (6-14\u00a0weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4+ T\u00a0cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.
\n \n\n \n \nBackgroundThe duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters.MethodsWe investigated the duration and effectiveness of immunity in a prospective cohort of asymptomatic health care workers in the United Kingdom who underwent routine polymerase-chain-reaction (PCR) testing. Vaccine effectiveness (\u226410 months after the first dose of vaccine) and infection-acquired immunity were assessed by comparing the time to PCR-confirmed infection in vaccinated persons with that in unvaccinated persons, stratified according to previous infection status. We used a Cox regression model with adjustment for previous SARS-CoV-2 infection status, vaccine type and dosing interval, demographic characteristics, and workplace exposure to SARS-CoV-2.ResultsOf 35,768 participants, 27% (9488) had a previous SARS-CoV-2 infection. Vaccine coverage was high: 97% of the participants had received two doses (78% had received BNT162b2 vaccine [Pfizer-BioNTech] with a long interval between doses, 9% BNT162b2 vaccine with a short interval between doses, and 8% ChAdOx1 nCoV-19 vaccine [AstraZeneca]). Between December 7, 2020, and September 21, 2021, a total of 2747 primary infections and 210 reinfections were observed. Among previously uninfected participants who received long-interval BNT162b2 vaccine, adjusted vaccine effectiveness decreased from 85% (95% confidence interval [CI], 72 to 92) 14 to 73 days after the second dose to 51% (95% CI, 22 to 69) at a median of 201 days (interquartile range, 197 to 205) after the second dose; this effectiveness did not differ significantly between the long-interval and short-interval BNT162b2 vaccine recipients. At 14 to 73 days after the second dose, adjusted vaccine effectiveness among ChAdOx1 nCoV-19 vaccine recipients was 58% (95% CI, 23 to 77) - considerably lower than that among BNT162b2 vaccine recipients. Infection-acquired immunity waned after 1 year in unvaccinated participants but remained consistently higher than 90% in those who were subsequently vaccinated, even in persons infected more than 18 months previously.ConclusionsTwo doses of BNT162b2 vaccine were associated with high short-term protection against SARS-CoV-2 infection; this protection waned considerably after 6 months. Infection-acquired immunity boosted with vaccination remained high more than 1 year after infection. (Funded by the U.K. Health Security Agency and others; ISRCTN Registry number, ISRCTN11041050.).
\n \n\n \n \nObjectiveThis study summarises nutritional intake among patients with tuberculosis (TB) along the Myanmar\u2013Thailand border according to the local diet.SettingTB clinic along the Myanmar\u2013Thailand border.ParticipantsCross-sectional surveys of 24-hour food recall were conducted with participants receiving anti-TB treatment. Participants were purposively selected to reflect proportion of age, sex and HIV co-infection based on historical patient records. Out of a total of 28 participants, 20 (71.4%) were men and 5 (17.9%) were co-infected with HIV.Primary and secondary outcome measuresThe primary outcome compared actual recorded intake to recommended intake. Secondary outcomes compared weight gain and body mass index (BMI) from diagnosis to time of survey.ResultsThere were no significant differences in macronutrient or micronutrient intake by sex or for patients supplementing their rations. Mean treatment length at time of survey was 20.7 weeks (95%\u2009CI: 16.5 to 24.8). A significantly higher proportion of women (8/8, 100%) met caloric requirements compared with men (9/20, 45.0%, p=0.010), but few participants met other macronutrient or micronutrient requirements, with no significant differences by sex or for patients supplementing their rations. From diagnosis to the time of the survey, participants averaged significant weight gain of 6.48\u2009kg (95%\u2009CI: 3.87 to 9.10) and increased BMI of 2.47 kg/m2 (95%\u2009CI: 1.45 to 3.49; p=0.0001 for both). However, 50% (14/28) still had mild or more severe forms of malnutrition.ConclusionsThis cross-sectional survey of nutritional intake in patients undergoing TB treatment in a sanatorium setting demonstrates the difficulty in sufficiently meeting nutritional demands, even when providing nutritional support.
\n \n\n \n \n